Iron Therapy, Advanced Oxidation Protein Products, and Carotid Artery Intima-Media Thickness in End-Stage Renal Disease

Abstract

Background-Increased common carotid artery intima-media thickness (CCA-IMT) is a marker of early atherosclerosis.Low-grade inflammation is associated with the pathogenesis of atherosclerosis. Low-grade inflammation and increased CCA-IMT are observed in end-stage renal disease (ESRD). Oxidative stress is involved in uremia-related inflammation. Advanced oxidation protein products (AOPP) are markers of oxidant-mediated protein damage in ESRD. Intravenous iron given to patients on hemodialysis (HD) might induce oxidative stress. We investigated the relationships between AOPP, iron therapy, and CCA-IMT in stable HD patients. Methods and Results-Plasma AOPP and blood chemistry, including iron status, were analyzed in a cohort of 79 ESRD patients on HD. Measurements of CCA-IMT and CCA diameter, as assessed by B-mode ultrasonography, were obtained in 60 patients. AOPP levels were elevated in ESRD patients, and in univariate (rϭ0.42, PϽ0.0001) and multivariate analyses (rϭ0.38, PϽ0.001), they correlated with serum ferritin and with the intravenous iron dose received during the 12 months preceding the study (ferritin, PϽ0001; AOPP, PϽ0.01). Univariate and multivariate analyses identified the AOPP concentration as being significantly associated with CCA-IMT (Pϭ0.0197) and CCA wall-to-lumen ratio (rϭ0.560, PϽ0.0001). Independently of AOPP concentration, cumulative iron dose was positively related to CCA-IMT (Pϭ0.015) in patients Ͻ60 years. Conclusion-In ESRD patients, CCA-IMT and CCA wall-to-lumen ratio were associated with plasma AOPP, serum ferritin, and the annual intravenous iron dose administered. These findings support the concept of a role of oxidative stress in the early atherosclerosis of ESRD patients, which may be increased by the usually recommended doses of intravenous iron.

An integrated system for the complete segmentation of the common carotid artery bifurcation in ultrasound images

“…We also found in this study, as well as in other studies performed by our group [7,15,32] an increase of carotid IMT with age and this is also in accordance with other studies [51,52] . This increase of IMT with age reflects a progression of athero/ arteriosclerotic changes following a natural ageing process.…”

Administration of Parenteral Iron and Mortality among Hemodialysis Patients

“…In part, we chose this approach because potential mechanisms by which it has been speculated that parenteral iron administration might lead to adverse outcomes include elevated risk of serious infection and increased oxidative stress leading to atheromatous change (6 -10). No clear epidemiologic links have been established between iron administration and an elevated population risk of either infection (11,12,28 -30) or atherosclerosis in ESRD or other populations (31)(32)(33)(34)(35)(36). However, the effect, if any, of iron dosing on mortality due to life-threatening infection most plausibly should be highest shortly after a dose and fall over time, whereas toxicity mediated through oxidative stress and atheromatous change may become clinically manifest only after a lag following iron administration.…”

Advanced Oxidation Protein Products Induce Vascular Calcification by Promoting Osteoblastic Trans-Differentiation of Smooth Muscle Cells via Oxidative Stress and ERK Pathway

“…[15] AOPPs are markers of oxidant-mediated protein damage, [16] and AOPP level is highly correlated to atherosclerotic cardiovascular events. [17,18] More importantly, AOPPs have been shown to directly cause oxidative damage to cells and tissues. Oxidative stress has also been shown to cause the smooth muscle cell to dedifferentiate.…”